Extracellular vesicle-mediated approaches for the diagnosis and therapy of MASLD: current advances and future prospective

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 7, 2025

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is an asymptomatic, multifaceted condition often associated with various risk factors, including fatigue, obesity, insulin resistance, metabolic syndrome, and sleep apnea. The increasing burden of MASLD underscores the critical need for early diagnosis effective therapies. Owing to lack efficient therapies MASLD, crucial. Consequently, noninvasive biomarkers imaging techniques are essential analyzing play a pivotal role in global diagnostic process. use extracellular vesicles has emerged as promising therapy ailments. Herein, comprehensive summary current modalities presented, highlighting their advantages limitations while exploring potential (EVs) innovative therapeutic tools MASLD. With this aim, review emphasizes in-depth understanding origin EVs pathophysiological alterations these ectosomes exosomes diseases. This also explores key components future management disease. dual utility essentially highlights clinical integration improve treatment. While EV-based still stages development require substantial research increase value before they can be used clinically, application been extensively explored. Moving forward, developing devices leveraging will crucial advancing diagnosis. Thus, literature summarized provides suitable grounds clinicians researchers explore devising treatment strategies

Language: Английский

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Human umbilical cord mesenchymal stem cells attenuate diet-induced obesity and NASH-related fibrosis in mice

Heliyon, Journal Year: 2024, Volume and Issue: 10(3), P. e25460 - e25460

Published: Feb. 1, 2024

Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) that may progress to cirrhosis and hepatocellular carcinoma but has no available treatment. Mesenchymal stem cells (MSCs) have become increasingly prominent in cell therapy. Human umbilical cord MSCs (hUC-MSCs) are considered superior other due their strong immunomodulatory ability, ease collection, low immune rejection, tumorigenicity. Though hUC-MSCs received increasing attention research, they been rarely applied any investigations or treatments NASH associated fibrosis. Therefore, this study evaluated the therapeutic efficacy C57BL/6 mice with diet-induced NASH. At week 32, were randomized into two groups: phosphate-buffered saline MSCs, which injected tail vein. 40, glucose metabolism was using insulin tolerance tests. NASH-related indicators examined various biological methods. hUC-MSC administration alleviated obesity, metabolism, hepatic steatosis, inflammation, Liver RNA-seq showed expression acyl-CoA thioesterase (ACOT) family members Acot1, Acot2, Acot3 involved acid altered. The cytochrome P450 (CYP) Cyp4a10 Cyp4a14, peroxisome proliferator-activator receptor (PPAR) signaling pathway, significantly downregulated after In conclusion, effectively reduced Western NASH, fibrosis mice, partly by regulating lipid PPAR pathway.

Language: Английский

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Roles of extracellular vesicles from different origins in metabolic-associated fatty liver disease: progress and perspectives

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 10, 2025

Metabolic-Associated Fatty Liver Disease (MAFLD) is the most common chronic liver disease worldwide, associated with systemic metabolic dysregulation. It can progress from simple hepatic steatosis (MAFL) to more severe conditions like Steatohepatitis (MASH), fibrosis, cirrhosis, and Hepatocellular Carcinoma (HCC). There a critical lack of reliable non-invasive diagnostic methods effective pharmaceutical treatments for MAFLD/MASH, emphasizing need further research. Extracellular vesicles (EVs) are nanoscale structures that play important roles in cell signaling by delivering bioactive molecules. However, there significant gap literature regarding EVs hosts, plants, microbiota MAFLD. This review explores potential various sources—host, microbiota—as biomarkers, therapeutic agents, drug carriers, treatment targets Firstly, host-derived extracellular MAFLD, focus on cell-type specific their components—proteins, miRNAs, lipids—for diagnosis monitoring were discussed. Moreover, it highlighted mesenchymal stem (MSC)-derived reducing lipid accumulation injury, immune cell-derived mitigating inflammation fibrosis. The also discussed use as carriers due ability deliver molecules impact mechanisms. Additionally, summarized research plant-derived EVs, which help reduce accumulation, inflammation, enhance gut barrier function Also, explored microbial-derived novel targets, particularly relation insulin resistance, dysfunction Overall, exploring diverse host, plant, sources this offers valuable insights into biomarkers strategies, could pave way options increasingly prevalent disease. Notably, challenges translating clinical practice thoroughly discussed, aiming provide possible directions strategies future

Language: Английский

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Apical papilla stem cell-derived exosomes regulate lipid metabolism and alleviate inflammation in the MCD-induced mouse NASH model

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 222, P. 116073 - 116073

Published: Feb. 21, 2024

Language: Английский

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Current perspectives on mesenchymal stem cells as a potential therapeutic strategy for non-alcoholic fatty liver disease

World Journal of Stem Cells, Journal Year: 2024, Volume and Issue: 16(7), P. 760 - 772

Published: July 25, 2024

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant health challenge, characterized by its widespread prevalence, intricate natural progression and multifaceted pathogenesis. Although NAFLD initially presents benign fat accumulation, it may progress to steatosis, non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma. Mesenchymal stem cells (MSCs) are recognized for their intrinsic self-renewal, superior biocompatibility, minimal immunogenicity, positioning them therapeutic innovation diseases. Therefore, this review aims elucidate the potential roles of MSCs in alleviating alteration underlying molecular pathways, including glycolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum fibrosis. The insights expected provide further understanding therapeutics, support development MSC-based therapy treatment NAFLD.

Language: Английский

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Tackling exosome and nuclear receptor interaction: an emerging paradigm in the treatment of chronic diseases

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: Sept. 26, 2024

Abstract Nuclear receptors (NRs) function as crucial transcription factors in orchestrating essential functions within the realms of development, host defense, and homeostasis body. NRs have garnered increased attention due to their potential therapeutic targets, with drugs directed at demonstrating significant efficacy impeding chronic disease progression. Consequently, these pharmacological agents hold promise for treatment management various diseases. Accumulating evidence emphasizes regulatory role exosome-derived microRNAs (miRNAs) inflammation, progression, therapy resistance, primarily by modulating factors, particularly NRs. By exploiting inflammatory pathways such protein kinase B (Akt)/mammalian target rapamycin (mTOR), nuclear factor kappa-B (NF-κB), signal transducer activator 3 (STAT3), Wnt/β-catenin signaling, exosomes play a pivotal panorama physiology, pathology. The internalization modulates initiates diverse autocrine or paracrine signaling cascades, influencing processes recipient cells survival, proliferation, differentiation, metabolism, cellular defense mechanisms. This comprehensive review meticulously examines involvement exosome-mediated NR regulation pathogenesis ailments, including atherosclerosis, cancer, diabetes, liver diseases, respiratory conditions. Additionally, it elucidates molecular intricacies communication between via NRs, leading immunomodulation. Furthermore, outlines implications exosome-modulated prophylaxis delineates current limitations, provides insights into future perspectives. also presents existing on components emergence resistance.

Language: Английский

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Current, emerging, and potential therapies for non-alcoholic steatohepatitis

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 30, 2023

Non-alcoholic fatty liver disease (NAFLD) has been identified as the most common chronic worldwide, with a growing incidence. NAFLD is considered hepatic manifestation of metabolic syndrome that emerges from multiple factors (e.g., oxidative stress, disorders, endoplasmic reticulum cell death, and inflammation). steatohepatitis (NASH), an advanced form NAFLD, reported to be leading cause cirrhosis carcinoma, it progressing rapidly. Since there no approved pharmacotherapy for NASH, considerable number therapeutic targets have emerged deepening research on NASH pathogenesis. In this study, potential properties regulating metabolism, gut microbiome, antioxidant, microRNA, inhibiting apoptosis, targeting ferroptosis, stem cell-based therapy in are reviewed evaluated. single-drug treatment affected by individual heterogeneous responses side effects, imperative precisely carry out targeted low toxicity. Lastly, agent delivery based exosomes proposed such drugs different mechanisms can incorporated generate high-efficiency low-toxicity individualized medicine.

Language: Английский

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Mesenchymal stromal/stem cells and their extracellular vesicles in liver diseases: insights on their immunomodulatory roles and clinical applications

Cell & Bioscience, Journal Year: 2023, Volume and Issue: 13(1)

Published: Sept. 5, 2023

Abstract Liver disease is a leading cause of mortality and morbidity that rising globally. dysfunctions are classified into acute chronic diseases. Various insults, including viral infections, alcohol or drug abuse, metabolic overload, may inflammation fibrosis, to irreversible liver dysfunction. Up now, transplantation could be the last resort for patients with end-stage disease. However, still faces unavoidable difficulties. Mesenchymal stromal/stem cells (MSCs) their broad ranging anti-inflammatory immunomodulatory properties can effectively used treating diseases but without limitation associated transplantation. In this review, we summarize discuss recent advances in characteristics MSCs potential action mechanisms MSCs-based cell therapies We also draw attention strategies potentiate therapeutic through pre-treatments gene modifications. Finally, progress toward clinical application extracellular vesicles

Language: Английский

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Model construction and drug therapy of primary ovarian insufficiency by ultrasound-guided injection

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 20, 2024

Abstract Background Clinically, hormone replacement therapy (HRT) is the main treatment for primary ovarian insufficiency (POI). However, HRT may increase risk of both breast cancer and cardiovascular disease. Exosomes derived from human umbilical cord mesenchymal stem cell (hUC-MSC) have been gradually applied to a variety diseases through inflammation inhibition, immune regulation, tissue repair functions. application study hUC-MSC exosomes in POI remain limited. Methods Here, we first constructed four rat animal models: POI-C model (the “cyclophosphamide-induced” via intraperitoneal injection), POI-B “busulfan-induced” model), POI-U under ultrasonic guidance), MS “maternal separation model”). Second, compared body weight, index, status, Rat Grimace Scale, complications, mortality rate different models. Finally, transabdominal ultrasound-guided injection was performed, its therapeuticy effects on models were evaluated, including changes levels, oestrous cycles, apoptosis fertility. In addition, performed RNA-seq explore possible mechanism function. Results Compared with POI-C, POI-B, models, showed less fluctuation lower fewer rate, higher success rate. successfully identified hUC-MSCs their exosomes, intraovarian injection. confirmed that exosome (termed POI-e) effectively improved cycle, function, Mechanically, play therapeutic role by regulating metabolic Conclusions our study, innovatively an drug method construct And efficacy Our will offer better choice new future provides certain guidance patients. Graphical abstract The schema construction extraction identifying Note: POI: premature insufficiency; hUC-MSCs: Human cells; POI-C: POI-cyclophosphamide; POI-B: POI-cyclophosphamide + Busulfan; POI-U: POI-Ultrasonic cyclophosphamide injection; MS: POI-Maternal separation. POI-e: AMH: Anti-müllerian hormone; LH: Luteinizing FSH: Follicle-stimulating DA: dopamine; T: Testosterone; PRL: prolactin; GnRH: Gonadotropin-releasing hormone.

Language: Английский

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Human adipose tissue-derived stem cell extracellular vesicles attenuate ocular hypertension-induced retinal ganglion cell damage by inhibiting microglia- TLR4/MAPK/NF-κB proinflammatory cascade signaling

Acta Neuropathologica Communications, Journal Year: 2024, Volume and Issue: 12(1)

Published: March 19, 2024

Abstract Microglia-mediated neuroinflammatory responses are recognized as a predominant factor during high intraocular pressure (IOP)-induced retinal and optic nerve injury along with potential therapeutic targets for the disease. Our previous research indicated that mesenchymal stem cell (MSC) treatment could reduce IOP-induced through TLR4 pathway in rat model without apparent replacement differentiation, suggesting anti-neuroinflammatory properties of MSCs potentially mediated by paracrine signaling. This study aimed to evaluate effect human adipose tissue-derived extracellular vesicles (ADSC-EVs) microbead-induced ocular hypertension (OHT) animals explore underlying mechanism since (EVs) primary transporters secretory action. The ADSC-EVs on LPS-stimulated BV-2 cells vitro OHT-induced vivo was investigated. According research, ADSC-EV reduced LPS-induced microglial activation TLR4/NF-κB proinflammatory cascade response axis cells, such CD68, iNOS, TNF-α, IL-6, IL-1β, TLR4, p-38 MAPK, NF-κB. data, intravitreal injection promoted RGC survival function, activation, microglial-derived responses, TLR4/MAPK/NF-κB OHT mice. findings provide preliminary evidence protective microglia-associated reduction effects inhibiting mice, indicating or adjunctive therapy glaucoma.

Language: Английский

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